Serum creatinine elevation following renin-angiotensin-aldosterone system blockade, adherence to monitoring and discontinuation guidelines, and long-term cardiorenal risks

Application Number
Lay Summary

Using large numbers of linked electronic health records in the UK, we will investigate whether guidelines for the use of a class of drugs commonly prescribed for conditions such as high blood pressure and heart problems (angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) are followed in every day clinical practice. Some patients experience a sudden decrease in kidney function after initiating these drugs. Such decreases should be captured by the general practitioner when comparing the kidney function before and after treatment start. However, previous data indicate that far from all patients have the necessary blood tests performed to evaluate such side effects. And if performed, it is unknown to what degree treatment is discontinued, and what consequences it holds for the patient’s long-term risk of chronic kidney disease, cardiovascular disease, and death. It is also important to investigate whether there are conditions, such as diabetes and previous heart attack, that influence these risks. Because ACE and ARBs are frequently used and the burden of kidney and cardiovascular disease severe, this study will have both public health and clinical importance.

Technical Summary

We will use the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) to identify all adult new users of ACEi/ARBs, who started treatment between April 1997 and March 2014 and who attended primary care practices contributing to CPRD. Among these patients, we will describe monitoring patterns, i.e., the proportion with pre- and post-initiation SCr measurements at different time points, average changes in SCr and electrolyte levels after initiation, and the proportion continuing treatment (receiving a 2nd or 3rd prescription) for different levels of increases. Among continuous ACEi/ARB users, we will then use Poisson regression, with adjustment for potential confounders, to estimate incidence rate ratios as measures of the association between categories of SCr increase and end-stage renal and cardiovascular diseases (myocardial infarction and heart failure). We will examine the robustness of our results through several sensitivity analyses and stratify on cardiorenometabolic comorbidities.

Health Outcomes to be Measured

First event during follow-up identified from HES and CPRD; end stage renal disease, worsening of renal function, myocardial infarction, heart failure, mortality (all-cause), and major adverse cardiovascular events (composite of death, myocardial infarction, and heart failure)


Laurie Tomlinson - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Morten Schmidt - Corresponding Applicant - Aarhus University Hospital
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Henrik Toft Sorensen - Collaborator - Aarhus University
Kathryn Mansfield - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Krishnan Bhaskaran - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )


HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation